We have three fundamental aims: (1) to examine relationships of structural brain characteristics determined at autopsy with clinical diagnoses, cognitive function, and motor function in the years and months prior to death, (2) to assess associations of candidate risk factors with incident mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VsD), extrapyramidal motor signs (EMS), and Parkinson's disease (PD), and (3) to estimate age-specific incidence rates for these same endpoints, extending existing estimates into the tenth decade of life. These will be accomplished by continuing operation of the Honolulu-Asia Aging Study (HAAS) through two full examination cycles, providing new cases for analysis in combination with recently identified incident cases. All accrued data and materials will be added to the existing NIA-Kuakini HAAS Archive, to be made available to collaborating scientists at the NIA and at other extramural sites, to 'facilitate preservation and future utilization of this unique resource. Our structure-function research is focused on 4 major, distinct, aging-related structural brain changes: the Alzheimer process (indicated by neurofibrillary tangles and neuritic plaques), cerebrovascular disease (infarcts and arterial wall architecture), aging-related atrophy (general and regional), and the Lewy body process (associated with nigral degeneration, PD, EMS, and cortical Lewy body disease). Each endpoint is envisioned as linked most strongly to one of these, with variable contributions from one or more of the others. The risk factor research will include: examination of factors previously identified as associated with prevalent endpoints for their associations with incident endpoints; a search for "new" risk factors using information collected between 1986-93; and evaluation of recent data from Polysomnography, tests of olfaction, and tests of reaction time as indicators of incipient or imminent AD or PD. A closely related NIA grant will support autopsy acquisition, conduct, and data management activities related to neuropathology from June 1, 2000 through May 30, 2005. NIA contract support of current HAAS operations is scheduled to end June 30, 2001.